A randomized,double‐blind,controlled study of ultrasound‐guided corticosteroid injection into the joint of patients with inflammatory arthritis

Objective

Most corticosteroid injections into the joint are guided by the clinical examination (CE), but up to 70% are inaccurately placed, which may contribute to an inadequate response. The aim of this study was to investigate whether ultrasound (US) guidance improves the accuracy and clinical outcome of joint injections as compared with CE guidance in patients with inflammatory arthritis.

Methods

A total of 184 patients with inflammatory arthritis and an inflamed joint (shoulder, elbow, wrist, knee, or ankle) were randomized to receive either US‐guided or CE‐guided corticosteroid injections. Visual analog scales (VAS) for assessment of function, pain, and stiffness of the target joint, a modified Health Assessment Questionnaire, and the EuroQol 5‐domain questionnaire were obtained at baseline and at 2 weeks and 6 weeks postinjection. The erythrocyte sedimentation rate and C‐reactive protein level were measured at baseline and 2 weeks. Contrast injected with the steroid was used to assess the accuracy of the joint injection.

Results

One‐third of CE‐guided injections were inaccurate. US‐guided injections performed by a trainee rheumatologist were more accurate than the CE‐guided injections performed by more senior rheumatologists (83% versus 66%; P = 0.010). There was no significant difference in clinical outcome between the group receiving US‐guided injections and the group receiving CE‐guided injections. Accurate injections led to greater improvement in joint function, as determined by VAS scores, at 6 weeks, as compared with inaccurate injections (30.6 mm versus 21.2 mm; P = 0.030). Clinicians who used US guidance reliably assessed the accuracy of joint injection (P < 0.001), whereas those who used CE guidance did not (P = 0.29).

Conclusion

US guidance significantly improves the accuracy of joint injection, allowing a trainee to rapidly achieve higher accuracy than more experienced rheumatologists. US guidance did not improve the short‐term outcome of joint injection.

     

Safety and efficacy of long‐term intraarticular steroid injections in osteoarthritis of the knee: A randomized,double‐blind,placebo‐controlled trial

Objective

To evaluate the safety and efficacy of long‐term intraarticular (IA) steroid injections for knee pain related to osteoarthritis (OA).

Methods

In a randomized, double‐blind trial, 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg (34 patients) or saline (34 patients) into the study knee every 3 months for up to 2 years. The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years. Measurements of minimum joint space width were performed by an automated computerized method on standardized fluoroscopically guided radiographs taken with the patient standing and with the knee in a semiflexed position. The clinical efficacy measure of primary interest was the pain subscale from the Western Ontario and McMaster Universities OA Index (WOMAC). Efficacy measures of secondary interest were the total score on the WOMAC, physician's global assessment, patient's global assessment, patient's assessment of pain, range of motion (ROM) of the affected knee, and 50‐foot walking time. Clinical symptoms were assessed just before each injection.

Results

At the 1‐year and 2‐year followup evaluations, no difference was noted between the two treatment groups with respect to loss of joint space over time. The steroid‐injected knees showed a trend toward greater symptom improvement, especially at 1 year, for the WOMAC pain subscale, night pain, and ROM values (P = 0.05) compared with the saline‐injected knees. Using area under the curve analyses, knee pain and stiffness were significantly improved throughout the 2‐year study by repeated injections of triamcinolone acetonide, but not saline (P < 0.05).

Conclusion

Our findings support the long‐term safety of IA steroid injections for patients with symptomatic knee OA. No deleterious effects of the long‐term administration of IA steroids on the anatomical structure of the knee were noted. Moreover, long‐term treatment of knee OA with repeated steroid injections appears to be clinically effective for the relief of symptoms of the disease.

     

Intraarticular corticosteroid injection for first carpometacarpal osteoarthritis

OBJECTIVE: To evaluate the efficacy of intraarticular corticosteroid injections for osteoarthritis (OA) of the first carpometacarpal (CMC) joint. METHODS: This was a prospective case series of patients presenting to a community rheumatology clinic with OA of the 1st CMC joint. A total of 0.25 ml of methylprednisolone acetate was injected into the 1st CMC joint in 25 patients, who were followed for one year. RESULTS: A significant improvement in the visual analog scale (VAS) for pain was noted at one month but not at 3, 6, or 12 months postinjection. However, 5 patients were pain-free at 12 months postinjection. Many patients noted improvement in tasks such as lifting a full cup and turning a faucet. Injections were well tolerated, with only 2 patients noting minor side effects. CONCLUSION: These results suggest that intraarticular corticosteroid injection for 1st CMC OA is a well tolerated procedure. A significant longterm benefit of corticosteroid injection for 1st CMC OA was not observed.     

A double blind,randomized, placebo controlled study to evaluate the efficacy of erythromycin in patients with knee effusion due to osteoarthritis

Objective: The efficacy of erythromycin in treatment of knee effusion due to osteoarthritis was evaluated. Method: We assessed efficacy and safety of erythromycin during 16 weeks in patients enrolled in a randomized double‐blind study. One hundred and eight patients with knee effusion due to osteoarthritis (OA) received 12‐week courses of erythromycin or placebo allocated randomly, and were followed for 4 months. Acetaminophen 650 mg/day was used in both groups, while they received no other anti‐inflammatory drugs (such as corticosteroid or nonsteroidal anti‐inflammatory drugs) during the course of the study. Our patients were divided in two groups, erythromycin in doses of 200 mg four times per day was given to the first group (51 patients) over the first 3 months of the study and in the second group we used placebo with the same dosage and schedule (53 patients). Outcomes improvement for the erythromycin‐treated group was assessed by a significantly higher mean score from baseline to the end of the trial, compared with placebo group. Patients were examined monthly during the treatment period. Measurement values included recording of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire subscales (pain, stiffness and function), range of motion and knee circumference. Results: Erythromycin produced a higher response rate than placebo in treatment of knee effusion due to OA. Significant reduction in knee circumference (P < 0.0005) and pain (P < 0.001) with functional improvement (P < 0.0005) were seen. At the first month after treatment, 11.8% (6 patients) in erythromycin and 9.4% (5 patients) in placebo groups had 50% pain reduction, which was not significant (P = 0.75). At the fourth month, 50% reduction of pain was seen in 45.1% (23 patients) of the erythromycin and 11.3% (6 patients) of the placebo group. This was statistically significant (P < 0.0005). Erythromycin treatment was well tolerated and mild adverse events caused no discontinuation during the study. Conclusion: This is a placebo‐controlled study of macrolid efficacy on knee effusion due to OA in a short period. Results of this research showed the better efficacy of erythromycin in controlling effusion and pain with functional improvement in patients with knee effusion due to OA.     

Prevalence of generalised osteoarthritis in patients with advanced hip and knee osteoarthritis: the Ulm Osteoarthritis Study

OBJECTIVES: Different prevalences of generalised osteoarthritis (GOA) in patients with knee and hip OA have been reported. The aim of this investigation was to evaluate radiographic and clinical patterns of disease in a hospital based population of patient subgroups with advanced hip and knee OA and to compare the prevalence of GOA in patients with hip or knee OA, taking potential confounding factors into account. METHODS: 420 patients with hip OA and 389 patients with knee OA scheduled for unilateral total joint replacement in four hospitals underwent radiographic analysis of ipsilateral and contralateral hip or knee joint and both hands in addition to a standardised interview and clinical examination. According to the severity of radiographic changes in the contralateral joints (using Kellgren-Lawrence > or = grade 2 as case definition) participants were classified as having either unilateral or bilateral OA. If radiographic changes of two joint groups of the hands (first carpometacarpal joint and proximal/distal interphalangeal joints defined as two separate joint groups) were present, patients were categorised as having GOA. RESULTS: Patients with hip OA were younger (mean age 60.4 years) and less likely to be female (52.4%) than patients with knee OA (66.3 years and 72.5% respectively). Intensity of pain and functional impairment at hospital admission was similar in both groups, while patients with knee OA had a longer symptom duration (median 10 years) compared with patients with hip OA (5 years). In 41.7% of patients with hip OA and 33.4% of patients with knee OA an underlying pathological condition could be observed in the replaced joint, which allowed a classification as secondary OA. Some 82.1% of patients with hip and 87.4% of patients with knee OA had radiographic changes in their contralateral joints (bilateral disease). The prevalence of GOA increased with age and was higher in female patients. GOA was observed more often in patients with knee OA than in patients with hip OA (34.9% versus 19.3%; OR = 2.24; 95% CI: 1.56, 3.21). Adjustment for the different age and sex distribution in both patient groups, however, takes away most of the difference (OR = 1.32; 95% CI: 0.89, 1.96). CONCLUSION: The crude results confirm previous reports as well as the clinical impression of GOA being more prevalent in patients with advanced knee OA than in patients with advanced hip OA. However, these different patterns might be attributed to a large part to a different distribution of age and sex in these hospital based populations.     

Intra-articular hyaluranic acid compared with progressive knee exercises in osteoarthritis of the knee: a prospective randomized trial with long-term follow-up

The goal of this study was to determine whether hyaluronic acid (HA) or progressive knee exercises (PE) can improve functional parameters in patients with osteoarthritis (OA) of the knee. In a prospective clinical trial 200 knees (105 patients) with radiographic Kellgren Lawrence grade III OA were randomized and received either three intra-articular injections of hyaluronic acid (Hylan G-F 20) at one-week intervals or PE for 6 weeks. Patients were evaluated by use of the Hospital for Special Surgery (HSS) Knee Score and followed-up for 18 months. Total HSS score for HA and PE patients improved from 62.6±13.8 to 88.8±11.1 and from 65.4±12.3 to 88.3±9.1, respectively, at the end of the trial (P<0.01). There were no statistically significant differences between the groups. Twenty-one patients of the HA group were excluded from the study because they had received another form of therapy. All patients in the PE group completed the trial. The patients who dropped out had also significant improvement from 57.0±12.9 to 76.7±11.9 (P<0.01). This prospective randomized trial confirmed that both HA injections and PE result in functional improvement. HA injections also increase the levels of satisfaction of the OA patients.     

Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized,double-blind,placebo-controlled trial

OBJECTIVE: To evaluate the safety and efficacy of long-term intraarticular (IA) steroid injections for knee pain related to osteoarthritis (OA). METHODS: In a randomized, double-blind trial, 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg (34 patients) or saline (34 patients) into the study knee every 3 months for up to 2 years. The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years. Measurements of minimum joint space width were performed by an automated computerized method on standardized fluoroscopically guided radiographs taken with the patient standing and with the knee in a semiflexed position. The clinical efficacy measure of primary interest was the pain subscale from the Western Ontario and McMaster Universities OA Index (WOMAC). Efficacy measures of secondary interest were the total score on the WOMAC, physician's global assessment, patient's global assessment, patient's assessment of pain, range of motion (ROM) of the affected knee, and 50-foot walking time. Clinical symptoms were assessed just before each injection. RESULTS: At the 1-year and 2-year followup evaluations, no difference was noted between the two treatment groups with respect to loss of joint space over time. The steroid-injected knees showed a trend toward greater symptom improvement, especially at 1 year, for the WOMAC pain subscale, night pain, and ROM values (P = 0.05) compared with the saline-injected knees. Using area under the curve analyses, knee pain and stiffness were significantly improved throughout the 2-year study by repeated injections of triamcinolone acetonide, but not saline (P < 0.05). CONCLUSION: Our findings support the long-term safety of IA steroid injections for patients with symptomatic knee OA. No deleterious effects of the long-term administration of IA steroids on the anatomical structure of the knee were noted. Moreover, long-term treatment of knee OA with repeated steroid injections appears to be clinically effective for the relief of symptoms of the disease.     

Higher doses of peginterferon alpha-2b administered twice weekly improve sustained virological response in difficult-to-treat patients with chronic hepatitis C: results of a pilot randomized study

Summary. Beside substantial progress in treatment of chronic hepatitis C (CHC) particular patients (genotype 1/4, high viral load, previous nonresponse, cirrhosis) remain difficult to treat. The aim of our pilot randomized study was to compare efficacy and tolerability of standard doses of Peginterferon alpha-2b + ribavirin with higher doses of Peginterferon alpha-2b administered twice weekly + ribavirin. Sixty-five outpatients with CHC were subsequently enrolled. Group A (n = 22) received recommended doses of Peginterferon alpha-2b and group B (n = 43), received high doses twice weekly. Groups were comparable for baseline characteristics. All genotype 1/4 patients had high baseline viraemia. Sustained virological response (SVR) was significantly higher in group B among naïve patients (72%vs 25%, P = 0.024). A significantly higher rate of SVR was observed in group B both considering only genotype 1/4 patients, (46%vs 13%, P = 0.03) and grouping together genotype 1/4 naive and relapsers (57%vs 11%, P = 0.039). Discontinuation rate was 32% (7 of 22) in group A and 19% (8 of 43) in group B. Our response rates are the highest reported for genotype 1/4 with high viraemia. Our pilot study supports the need of randomized studies to evaluate both viral kinetics and efficacy of high dose and twice weekly administration of Peginterferon alpha-2b in genotype 1/4 patients with high viraemia who may need personalized treatment schedules.     

Colonoscopy in elderly Asians: a prospective evaluation in routine clinical practice

OBJECTIVE: Colonoscopy is believed to be more complicated in elderly patients in Western countries. It is uncertain if the situation holds true among Asians. This study is to determine differences in colonoscopy performance and sedation complications between patients aged <65 years and those ≥65 years of age in an Asian population. METHODS: A prospective, cross‐sectional study of adults attending outpatient colonoscopy at a tertiary institution. Clinical and endoscopic data were obtained from all consenting adults. RESULTS: Two hundred and one patients (70 elderly and 131 aged <65 years) were enrolled. Compared to the patients aged <65 years, the elderly patients had similar levels of good (42.9%vs 45.8%), satisfactory (42.9%vs 33.6%) and poor (14.3%vs 20.6%) bowel preparations (P = NS). Cecal intubation was achieved in 60 (85.7%) of the elderly patients and 116 (88.5%) of the younger adults (P = NS). The differences in mean total colonoscopy duration was not significant (30 ± 13 vs 27 ± 11 min). Although the elderly patients received lower mean sedation doses of midazolam (4.7 vs 5.1 mg) and pethidine (37.8 vs 46.4 mg) compared to the younger adults, the hypotension rates were significantly higher in the elderly patients (7.1%vs 0.8%, P = 0.01). The elderly patients had in additional one or more co‐morbid illnesses (P = 0.001), with significantly higher rates of diabetes (P = 0.004), ischemic heart disease (P = 0.03), hypertension (P = 0.001) and stroke disease (P = 0.004). CONCLUSION: Colonoscopy performance in elderly Asians is similar to that in younger adults. However, the conscious sedation of these patients results in a higher rate of cardio‐vascular complications.     

Pilot study of the effects of a heat‐retaining knee sleeve on joint pain,stiffness, and function in patients with knee osteoarthritis

Objective

To identify changes in joint pain, stiffness, and functional ability in patients with knee osteoarthritis (OA) after use of a knee sleeve that prevents loss of body heat by the joint.

Methods

Subjects with symptomatic knee OA (n = 52) were randomized to 2 treatment groups: verum sleeve (specially fabricated to retain body heat) or placebo sleeve (standard cotton/elastane sleeve). Subjects wore the sleeve over the more painful OA knee for at least 12 hours daily for 4 weeks. Pain, stiffness, and functional impairment (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) in the index knee were measured at baseline and after 4 weeks of wear, after which sleeve use was discontinued. Telephone followup interviews were conducted 2 and 4 weeks later.

Results

After 4 weeks of sleeve wear, subjects in the active treatment group reported a 16% decrease in mean WOMAC pain score relative to baseline (P = 0.001). Those who wore the placebo sleeve reported a 9.7% decrease from baseline (P = 0.002). The difference between treatment groups was not statistically significant (P = 0.12). However, it was found that the 12 subjects who believed correctly that they had received the verum sleeve reported a highly significant decrease in WOMAC pain score (?27.5% relative to baseline, P = 0.0001). In comparison, subjects who received the verum sleeve but believed they had received the placebo sleeve exhibited only a marginally significant improvement in pain (?13.0% relative to baseline, P = 0.07). In the placebo group, the modest improvement in pain scores appeared unrelated to the subject's impression of the type of sleeve worn.

Conclusion

This pilot study was insufficiently powered to be a definitive trial of the heat‐retaining sleeve. Given the magnitude of changes in knee pain in the active treatment group, heat retention merits further scientific investigation as a treatment modality for patients with knee OA.

     

Ultrasound of the knee during voluntary quadriceps contraction: A technique for detecting otherwise occult effusions

Objective

To describe 1) a technique that can detect synovial effusions not seen on static ultrasound (US) examination and 2) the characteristics of patients with knee osteoarthritis (OA) for whom this technique proved useful.

Methods

From reviewed records of 76 patients with knee OA (112 knees) that we had seen for US‐guided injections over a defined period, we found 45 knees with no detectable effusion on static US, of which 18 (14 patients) showed fluid when scanned during voluntary quadriceps contraction. For all patients, we had recorded effusion features (physical examination, presence and size on US), and success of joint entry was determined by getting synovial fluid and/or seeing an air echo or inflow of injected material.

Results

The 14 patients we studied were obese (mean ± SEM body mass index 32.7 ± 2.3 kg/m²; 3 morbidly obese), with moderate to severe OA by radiography in most (Kellgren/Lawrence class 3 or 4 in 10 of 14 knees for which radiographs were available). The suprapatellar synovial space seen by US was small (mean ± SEM depth 0.38 ± 0.04 cm). Arthrocentesis obtained 0.5–16 ml of synovial fluid (mean ± SEM 2.9 ± 0.6 ml), which correlated with the depth of effusion as seen on US with the quadriceps in maximum contraction (Spearman's ρ = 0.5597, P = 0.0157). In 4 knees where arthrocentesis failed to retrieve fluid, we observed at injection the inflow of material and a linear air echo.

Conclusion

US of the knee during voluntary quadriceps contraction can find effusions not detectable on static US. Such effusions provide targets for accurate aspiration and injection that would not be appreciated with static US.     

Effect of combination therapy with ribavirin and high-dose interferon-α2b for 24 weeks in chronic hepatitis C

Background and Aim: The aim of the present study was to determine whether a 24‐week course of combination therapy with ribavirin and high‐dose interferon‐α2b (IFN‐α2b) could provide an acceptable treatment efficacy in chronic hepatitis C (CHC). Methods: Seventy‐six patients with CHC whose serum hepatitis C virus (HCV) RNA levels were more than 100 kIU/mL on quantitative polymerase chain reaction (PCR) assay were included. The patients were assigned to two different dose groups of IFN‐α2b: group A (n = 39) received 6 MU and group B (n = 37) received 10 MU. Each group received the dose daily for 14 days then three times per week for a total of 24 weeks. In addition, HCV genotype 1b patients in group A and group B were classified into group C (n = 20) and D (n = 29), respectively. All patients received 600 or 800 mg ribavirin per day. Results: Sustained response rates in group A were significantly higher than those in group B (66.7%vs 35.1%, intent‐to‐treat, P = 0.0060). However, sustained response rates in group C were not different from those in group D (45.0%vs 20.7%, intent‐to‐treat, P = 0.0696). The proportion of patients who discontinued the treatment or reduced drug dosage because of adverse events was significantly higher in group B than in group A (27.0%vs 7.69%, P = 0.0224). Conclusion: A 24‐week course of combination therapy with ribavirin and 6 MU IFN‐α2b had an acceptable efficacy with fewer adverse events than that with ribavirin and 10 MU IFN‐α2b in CHC.     

Proprioception,dynamic balance and maximal quadriceps strength in females with knee osteoarthritis and normal control subjects

Background: Osteoarthritis (OA) is one of the most common musculoskeletal complaints worldwide. The knee is the most frequently involved joint of the lower limb in OA. Knee joint proprioception, dynamic balance and maximal quadriceps strength may be impaired in patients with knee OA. Objective: To investigate whether females with knee OA have reduced knee joint proprioception, balance responses and quadriceps strength compared with normal controls. Methods: We undertook a cross‐sectional study of 30 females with knee OA and 30 controls. Knee joint proprioception was measured using electrogoniometer. Dynamic balance response was determined using a step test. Quadriceps strength was measured isometrically using a modified Tornvall chair. Results: Subjects with OA had greater mean error, poorer dynamic balance and less quadriceps strength than non‐symptomatic ones (P < 0.001). Increasing age was associated with a decline in proprioceptive acuity for both controls and patients (r = 0.40, P < 0.001). In subjects with knee OA, decreased dynamic balance was associated with increasing weight (r = 0.30, P < 0.001) and reduced quadriceps strength (r = –0.37, P = 0.002). Conclusion: Compared with age and sex‐matched controls, females with symptomatic knee OA have reduced knee proprioception, balance responses and quadriceps strength.     

Efficacy and safety of 0.4 percent sodium hyaluronate for endoscopic submucosal dissection of gastric neoplasms

AIM:To evaluate the efficacy and safety of sodium hyaluronate solution(SH) in endoscopic submucosal dissection(ESD) of gastric neoplasms.METHODS:A prospective multicenter randomized,double blind,controlled trial was designed and utilized in this study.A total of 76 patients with 5-20 mm sized gastric neoplasms were enrolled at three academic hospitals in South Korea from June 2011 to October 2011.Patients were randomly assigned to the 0.4% sodium hyaluronate or control groups.All lesions underwent endoscopic ESD.ESD was performed with 0.4%SH and normal saline(NS) solution for submucosal injection.Efficacy was assessed using en bloc resection and the number of additional injections.Secondary evaluation variables were the volume of injection material,steepness of mucosal elevation,bleeding rate,procedural time and operator satisfaction.Finally,the safety was assessed by analyzing adverse events during the study.RESULTS:The usefulness rate in the 0.4%SH group and the controlled group had statistically significant difference under intention to treat(ITT) analysis(90.91% vs 61.11% P = 0.0041).Under per protocol(PP),the usefulness rate is statistically significant different(93.10% vs 61.76%,P = 0.0036).The difference in volume of the solution injected between 0.4%SH group and the controlled group and NS group was also statistically significant under intention to treat and per protocol analysis(ITT:0.03 ± 0.02 mL vs 0.06 ± 0.03 mL,P = 0.0003,PP:0.03 ± 0.02 mL vs 0.06 ± 0.03 mL,P = 0.0004).Satisfaction above the grade good was significantly higher in the SH group under intention to treat and per protocol analysis(ITT:90.91% vs 61.11%,P = 0.0041,PP = 93.11% vs 61.77%,P = 0.0022).Adverse events above grade 3 were not noticed in either group.All adverse events were treated and were judged as not associated with the submucosal injection solutions.CONCLUSION:0.4%SH solution is a safe and effective agent that doesn’t cause any significant adverse events and is useful for submucosal injection during ESD.     

Serum hyaluronic acid level as a predictor of disease progression in osteoarthritis of the knee

Objective. To investigate the prognostic value of serum hyaluronic acid (HA) and keratan sulfate (KS) levels in relation to tibiofemoral osteoarthritis (OA) of the knee. Methods. Clinical and demographic data were collected on 94 patients. Radiographs were obtained at study entry and at 5-year followup. Disease progression was defined as 2 mm of joint space narrowing of any tibiofemoral compartment, and/or knee joint surgery during the study period. Serum HA and KS were measured and levels were correlated with entry data and disease progression. Results. At entry, HA levels were significantly related to disease duration (P = 0.036), minimum joint space (P = 0.049), and previous surgery (P = 0.001). After these variables were taken into account, patients whose disease had progressed were shown to have had significantly higher levels of HA at baseline compared with those whose disease had not progressed (P = 0.019). However, there were no significant differences in levels of serum KS between those with and those without disease progression, at entry (P = 0.779) or at subsequent visits. Conclusion. These results suggest that serum HA levels predict disease outcome in OA of the knee and confirm that a single measurement of the serum level of KS is not useful as a prognostic marker in OA.     

Characterization of human synovial fluid cells of 26 patients with osteoarthritis knee for cartilage repair therapy

Aim: To investigate the possibility of chondrogenic differentiation and cartilage repair of synovial fluid cells of osteoarthritis (OA) knee. Methods: Synovial fluids from 26 patients with OA knee were aspirated from each knee joint and cultured in vitro. The morphology of cultured synovial fluid cells, cell proliferation rate, the phenotype, and chondrogenic differentiation were analyzed in in vitro. Also, human autologous synovial fluid cells were transplanted to OA cartilage, and the cells were traced in ex vivo. Results: In 19 of 26 materials, the cells proliferated satisfactorily. The cell proliferation in six materials was very slow and one material contaminated. Culture‐expanded synovial fluid cells had a fibroblastic morphology and the phenotype was negative for CD10, CD14, and CD45, and positive for CD13, CD44, and CD105. Pellet culture of synovial fluid cells showed chondrogenic differentiation. In the ex vivo study, autologous transplanted synovial fluid cells were observed in repaired or enhanced regenerative cartilage areas and showed a tendency to infiltrate the original degenerative cartilage of OA. Conclusions: This study proved the possibility of chondrogenic differentiation of synovial fluid cells of OA knee joints despite the pathologic environment within a diseased joint. Synovial fluid cells were actually heterogeneous cells but they showed chondrogenic differentiation, similar to that of bone marrow‐derived mesenchymal progenitor cells (BMMPCs). The Ex vivo study suggested that synovial fluid cells had a tendency to adhere to OA degenerative cartilage in humans.     

Local Deposition of Calcium Pyrophosphate Crystals in Evolution of Knee Osteoarthritis

The aim of the study was to investigate the frequency of development of local calcium pyrophosphate (CPPD) crystal deposition in patients with knee OA initially found negative for these crystals, as well as to discover whether prognostic indicators for this subset of patients can be found. A clinical follow-up of records of outpatients with idiopathic knee OA was established. An anteroposterior plain radiography of the knee joints was made initially and at the end of the observation period. The follow-up period needed to be more than 1 year. Patients were divided into two groups. The first included patients with knee OA who did not develop intra-articular CPPD crystal deposition during the observation period (OA group). The second included those patients whose X-rays or synovial fluid (SF) analysis in the follow-up showed these crystal deposits to be present (OA + CPPD group). There were 59 patients (42 women, 17 men) who met the selection criteria. During the observation period (8.1 ± 7.4 years in the OA group, 10.4 ± 6 years in the OA + CPPD group), intra-articular CPPD deposits were observed in 15 patients (25%): 10 on the X-rays, eight in the SF and three in both examinations. Age at diagnosis of OA and incidence of obesity were similar in both groups. There was a trend (P= 0.21) towards men developing intra-articular CPPD crystal deposits more frequently than women. OA in only one knee joint was significantly more frequent in the group with CPPD (P<0.01). Of those with CPPD deposits 40% required surgery at the end of the observation period, compared to 27.2% of those without deposits (P= 0.27). The waiting period before knee surgery was shorter in the OA + CPPD group but the difference was not statistically significant. In conclusion, local CPPD crystal deposition was observed in 25% of cases during the evolution of knee OA. No predictive factors were found. OA of the knee could, per se, favour the development of CPPD deposits. The occurrence of intra-articular CPPD deposits seemed to be related to a more rapid and severe evolution of OA of the knee. Received: 25 October 2000 / Accepted: 18 June 2001     

Intraarticular injection of anakinra in osteoarthritis of the knee: A multicenter,randomized, double‐blind,placebo‐controlled study

Objective

To evaluate the clinical response, safety, and tolerability of a single intraarticular injection of anakinra in patients with symptomatic osteoarthritis (OA) of the knee.

Methods

Patients with OA of the knee were enrolled in a multicenter, double‐blind, placebo‐controlled study and randomized 2:1:2 to receive a single intraarticular injection of placebo, anakinra 50 mg, or anakinra 150 mg in their symptomatic knee. Patients were evaluated for 12 weeks postinjection. The primary end point was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline to week 4. Safety assessments included the evaluation of adverse events (AEs), laboratory tests, and vital signs. Pharmacokinetic parameters were assessed in a subset of patients.

Results

Of 170 patients who enrolled, 160 (94%) completed the study. The mean improvements from baseline to week 4 in the WOMAC score were not statistically different between the placebo group and the patients who received 50 mg of anakinra (P = 0.67) or 150 mg of anakinra (P = 0.77). Anakinra was well tolerated. No withdrawals due to AEs or serious AEs, and no serious infections or deaths were reported. No clinically significant trends were noted in laboratory values or vital signs. Pharmacokinetic parameters demonstrated that the mean terminal half‐life of anakinra in serum after intraarticular injection was ∼4 hours.

Conclusion

Anakinra was well tolerated as a single 50‐mg or 150‐mg intraarticular injection in patients with OA of the knee. However, anakinra was not associated with improvements in OA symptoms compared with placebo.

     

The safety and efficacy of intraarticular hyaluronan with/without corticosteroid in knee osteoarthritis: 1-year, single-blind, randomized study

The goal of this study was to assess the safety and efficacy of hyaluronan (HA) with/without corticosteroid in patients with knee osteoarthritis (OA). In a 1-year, randomized, single-blind trial, 24 patients were treated with HA weekly for 3 weeks, then three injections on the 6th month for a total of six injections. Sixteen patients were treated the same but with the addition of 1 ml triamcinolone acetonide prior to the first and fourth HA injection. The treatment was repeated at the sixth month. The patients were evaluated with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the visual analog pain scale (VAS). After 1 year, progression of OA was evaluated with magnetic resonance imaging (MRI). During the study, pain relief was marked in patients who received combined treatment with respect to WOMAC pain and VAS (p<0.05). At the first year, no progression was observed in either treatment group. Although all patients had improvement for both pain and function, HA together with corticosteroid was superior to HA alone for early pain relief. The MRI findings showed that neither treatment showed a progression on the damage of the cartilage.     

KNEE PAIN AMONGST THE POOR AND AFFLUENT IN PAKISTAN

The frequency of joint symptoms was determined amongst 2022affluent and 2210 poor adults in Karachi, Pakistan. Joint painwas significantly (P = 0.025) more common amongst the affluent(6.6%) compared with the poor (5%) and this was due to a significantlygreater frequency of knee pain in the richer community (3% vs1.8%; P =0.008). The prevalence increased with age and was morecommon in females. Almost half were associated with varus deformity,suggesting the presence of associated OA in a high proportion.The overall frequency of knee pain seemed no greater than inseries reported from the West. Compared with age- and sex-matchedcontrols, body weight was significantly greater amongst thosewith knee pain, both amongst the affluent (P = 0.005) and thepoor (P = 0.02). Control subjects were heavier in the affluentpopulation, suggesting that the greater frequency of knee symptomsin this community was due to their relative obesity. Knee bendingat prayer was most common amongst the affluent controls andmay indicate that religious observance also contributed to theproblem in the richer population. Squatting was a characteristicof the poor who had less knee pain than the affluent. Knee flexingcould not therefore be confidently implicated. No relationshipcould be demonstrated between knee pain and joint laxity. KEY WORDS: Knee pain, Osteoarthritis, Pakistan, Obesity, Knee flexing, Joint laxity